Application of the DP4 Probability Method to Flexible Cyclic Peptides with Multiple Independent Stereocenters: The True Structure of Cyclocinamide A.
Ontology highlight
ABSTRACT:
SUBMITTER: Cooper JK
PROVIDER: S-EPMC6054539 | biostudies-literature | 2018 Jul
REPOSITORIES: biostudies-literature
Publications
Application of the DP4 Probability Method to Flexible Cyclic Peptides with Multiple Independent Stereocenters: The True Structure of Cyclocinamide A.
Cooper Jason K JK Li Kelin K Aubé Jeffrey J Coppage David A DA Konopelski Joseph P JP
Organic letters 20180709 14
A DP4 protocol has been successfully utilized to establish the true structure of the natural product cyclocinamide A, a flexible cyclic peptide with four isolated stereocenters. Benchmarking the necessary level of theory required to successfully predict the NMR spectra of three previously synthesized isomers of cyclocinamide A led to the prediction of the natural stereochemistry as 4 S, 7 R, 11 R, 14 S, which has been confirmed by total synthesis. ...[more]
Similar Datasets
Project description:While a new therapeutic cyclic peptide is approved nearly every year, docking large macrocycles has remained challenging. Here, we present a new version of our peptide docking software AutoDock CrankPep (ADCP), extended to dock peptides cyclized through their backbone and/or side chain disulfide bonds. We show that within the top 10 solutions, ADCP identifies the proper interactions for 71% of a data set of 38 complexes, thus making it a useful tool for rational peptide-based drug design.
| S-EPMC7737999 | biostudies-literature
Project description:Mechanical forces shape physiological structure and function within cell and tissue microenvironments, during which cells strive to restore their shape or develop an adaptive mechanism to maintain cell integrity depending on strength and type of the mechanical loading. While some cells are shown to experience permanent plastic deformation after a repetitive mechanical tensile loading and unloading, the impact of such repetitive compression on deformation of cells is yet to be understood. As such, the ability to apply cyclic compression is crucial for any experimental setup aimed at the study of mechanical compression taking place in cell and tissue microenvironments. Here, we demonstrate such cyclic compression using a microfluidic compression platform on live cell actin in SKOV-3 ovarian cancer cells. Live imaging of the actin cytoskeleton dynamics of the compressed cells was performed for varying pressures applied sequentially in ascending order during cell compression. Additionally, recovery of the compressed cells was investigated by capturing actin cytoskeleton and nuclei profiles of the cells at zero time and 24 h-recovery after compression in end point assays. This was performed for a range of mild pressures within the physiological range. Results showed that the phenotypical response of compressed cells during recovery after compression with 20.8 kPa differed observably from that for 15.6 kPa. This demonstrated the ability of the platform to aid in the capture of differences in cell behaviour as a result of being compressed at various pressures in physiologically relevant manner. Differences observed between compressed cells fixed at zero time or after 24 h-recovery suggest that SKOV-3 cells exhibit deformations at the time of the compression, a proposed mechanism cells use to prevent mechanical damage. Thus, biomechanical responses of SKOV-3 ovarian cancer cells to sequential cyclic compression and during recovery after compression could be revealed in a flexible microdevice. As demonstrated in this work, the observation of morphological, cytoskeletal and nuclear differences in compressed and non-compressed cells, with controlled micro-scale mechanical cell compression and recovery and using live-cell imaging, fluorescent tagging and end point assays, can give insights into the mechanics of cancer cells.
| S-EPMC9815655 | biostudies-literature
Project description:Cyclic peptides extend the druggable target space due to their size, flexibility, and hydrogen-bonding capacity. However, these properties impact also their passive membrane permeability. As the "journey" through membranes cannot be monitored experimentally, little is known about the underlying process, which hinders rational design. Here, we use molecular simulations to uncover how cyclic peptides permeate a membrane. We show that side chains can act as "molecular anchors", establishing the first contact with the membrane and enabling insertion. Once inside, the peptides are positioned between headgroups and lipid tails─a unique polar/apolar interface. Only one of two distinct orientations at this interface allows for the formation of the permeable "closed" conformation. In the closed conformation, the peptide crosses to the lower leaflet via another "anchoring" and flipping mechanism. Our findings provide atomistic insights into the permeation process of flexible cyclic peptides and reveal design considerations for each step of the process.
| S-EPMC9969412 | biostudies-literature
Project description:The demand for better "true performance" of supercapacitors, which is defined as the energy density based on the packaged cell with high active mass loading, is spurred by the ever-increasing energy storage market. The true performance of present supercapacitors is unsatisfactory, greatly limited by the currently used current collectors. Here, we develop a through-pore structured nickel current collector with excellent flexibility by electrodepositing nickel on laser-drilled stainless steel sheets filled with epoxy resin. Based on the new current collector, the electrodes possess higher performance than those fabricated by employing conventional current collectors. At a high active mass loading, the assembled supercapacitors show superior flexibility and high energy densities of 50.4 W hr L-1 and 30.1 W hr kg-1, respectively, based on the packaged cell, outperforming the present supercapacitors. Our strategy provides a new opportunity for promoting the further development of supercapacitors by enhancing the true performance.
| S-EPMC6215974 | biostudies-literature
Project description:To identify differentially expressed genes that dictates the cell uptake activity
2023-06-01 | GSE202764 | GEO
Project description:For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.
| S-EPMC5693220 | biostudies-literature
Project description:Episodic memory involves flexible retrieval processes that allow us to link together distinct episodes, make novel inferences across overlapping events, and recombine elements of past experiences when imagining future events. However, the same flexible retrieval and recombination processes that underpin these adaptive functions may also leave memory prone to error or distortion, such as source misattributions in which details of one event are mistakenly attributed to another related event. To determine whether the same recombination-related retrieval mechanism supports both successful inference and source memory errors, we developed a modified version of an associative inference paradigm in which participants encoded everyday scenes comprised of people, objects, and other contextual details. These scenes contained overlapping elements (AB, BC) that could later be linked to support novel inferential retrieval regarding elements that had not appeared together previously (AC). Our critical experimental manipulation concerned whether contextual details were probed before or after the associative inference test, thereby allowing us to assess whether (a) false memories increased for successful versus unsuccessful inferences, and (b) any such effects were specific to after compared with before participants received the inference test. In each of 4 experiments that used variants of this paradigm, participants were more susceptible to false memories for contextual details after successful than unsuccessful inferential retrieval, but only when contextual details were probed after the associative inference test. These results suggest that the retrieval-mediated recombination mechanism that underlies associative inference also contributes to source misattributions that result from combining elements of distinct episodes. (PsycINFO Database Record
| S-EPMC5334182 | biostudies-literature
Project description:The volume of securely encrypted data transmission increases continuously in modern society with all things connected. Towards this end, true random numbers generated from physical sources are highly required for guaranteeing security of encryption and decryption schemes for exchanging sensitive information. However, majority of true random number generators (TRNGs) are mechanically rigid, and thus cannot be compatibly integrated with some specific flexible platforms. Herein, we present a flexible and stretchable bionic TRNG inspired by the uniqueness and randomness of biological architectures. The flexible TRNG film is molded from the surface microstructures of natural plants (e.g., ginkgo leaf) via a simple, low-cost, and environmentally friendly manufacturing process. In our proof-of-principle experiment, the TRNG exhibits a fast generation speed of up to 1.04 Gbit/s, in which random numbers are fully extracted from laser speckle patterns with a high extraction rate of 72%. Significantly, the resulting random bit streams successfully pass all randomness test suites including NIST, TestU01, and DIEHARDER. Even after 10,000 times cyclic stretching or bending tests, or during temperature shock (-25-80 °C), the bionic TRNG still reveals robust mechanical reliability and thermal stability. Such a flexible TRNG shows a promising potential in information security of emerging flexible networked electronics.Electronic supplementary materialSupplementary material (light path diagram of transmitted laser speckle, pseudo random pattern, statistical distribution of bionic microstructures, haze of the bionic TRNG film, multi-layer circular laser intensity pattern, percentage of bit 0/1 for different hashed images, Pearson correlation coefficient between 100 different speckle images, the whole process of randomness extraction, SEM images of the flexible TRNG film after 10,000 times stretching and bending, continuous work stability of the TRNG at low or high temperature, light path diagram of reflective laser speckle, and detailed randomness test results of NIST, TestU01, and DIEHARDER) is available in the online version of this article at 10.1007/s12274-022-4109-9.
| S-EPMC8902273 | biostudies-literature
Project description:Cyclic peptides are widespread throughout the plant kingdom, and display diverse sequences, structures and bioactivities. The potential applications attributed to these peptides and their unusual biosynthesis has captivated the attention of researchers for many years. Several gene sequences for plant cyclic peptides have been discovered over the last two decades but it is only recently that we are beginning to understand the intricacies associated with their biosynthesis. Recent studies have focussed on three main classes of plant derived cyclic peptides, namely orbitides, SFTI related peptides and cyclotides. In this mini-review, we discuss the expansion of the known sequence and structural diversity in these families, insights into the enzymes involved in the biosynthesis, the exciting applications which includes a cyclotide currently in clinical trials for the treatment of multiple sclerosis, and new production methods that are being developed to realise the potential of plant cyclic peptides as pharmaceutical or agricultural agents.
| S-EPMC8286818 | biostudies-literature
Project description:Heterocycle-containing cyclic peptides are promising scaffolds for the pharmaceutical industry but their chemical synthesis is very challenging. A new universal method has been devised to prepare these compounds by using a set of engineered marine-derived enzymes and substrates obtained from a family of ribosomally produced and post-translationally modified peptides called the cyanobactins. The substrate precursor peptide is engineered to have a non-native protease cleavage site that can be rapidly cleaved. The other enzymes used are heterocyclases that convert Cys or Cys/Ser/Thr into their corresponding azolines. A macrocycle is formed using a macrocyclase enzyme, followed by oxidation of the azolines to azoles with a specific oxidase. The work is exemplified by the production of 17 macrocycles containing 6-9 residues representing 11 out of the 20 canonical amino acids.
| S-EPMC4282754 | biostudies-literature